The proposed continuation study is designed to leverage information from our prior comprehensive characterization of subsets of hair follicle (HF) melanocyte stem cells (McSCs); to determine how a subset of skin-derived stem cells exhibiting the potential to myelinate neurons can be isolated from mammalian skin and utilized therapeutically. The rationale for the study is based upon our prior work demonstrating that CD34+ McSCs, located in the HF bulge, exhibit a neural crest stem cell phenotype and expression profile; and are not exclusively committed to melanocyte differentiation. By separating CD34+ McSCs from other cells in the murine HF and skin, we have been able to characterize the genome-wide expression profile and functional characteristics of CD34+ McSCs; which include their ability to form myelin sheaths surrounding neurons. By applying this information to identify other skin-derived stem cells with similar properties that can be isolated de novo; we believe that we can develop approaches to treat demyelinating disease and the effects of neurological trauma with highly-specific and selected skin-derived stem cells. The objectives of our studies are to: 1) apply specific markers of CD34+ McSCs to murine and human skin-derived stem cells with neural crest differentiation properties, or skin-derived precursors (SKPs), and 2) to identify specific subsets of SKPs with glial properties. An additional objective is to determine whether CD34+ McSCs, along with specific SKP subsets subsequently identified, support neural repair in an established neural injury model. These studies will be accomplished using individual and core laboratory facilities in both the Baltimore VA Medical Center and in the University of Maryland School of Medicine. The results of these studies should have a positive impact on the health care of Veterans. Our comprehensive genomic and functional characterization of CD34+ McSCs may enable a strategy for identifying a highly-specific stem cell population from human skin- useful for supporting Veteran recovery from neurological injury and neurodegenerative disease.